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Prothrombin factor complex

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https://www.readbyqxmd.com/read/29785470/four-factor-prothrombin-complex-concentrate-for-warfarin-reversal-in-patients-with-left-ventricular-assist-devices
#1
Jessica Rimsans, Amy Levesque, Erin Lyons, Katelyn Sylvester, Michael M Givertz, Mandeep R Mehra, Garrick C Stewart, Jean M Connors
Continuous flow left ventricular assist devices (CF-LVAD) require therapeutic anticoagulation which is often interrupted for procedures or bleeding. Prior to the availability of four factor prothrombin complex concentrate (4F-PCC) in the United States, warfarin was held and its effects reversed by vitamin K or fresh frozen plasma. We evaluated the use of 4F-PCC for temporary warfarin reversal in patients with CF-LVADs and assessed outcomes. This analysis is a retrospective study of CF-LVAD patients who received 4F-PCC for warfarin reversal in the setting of bleeding or need for urgent or elective procedures...
May 21, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29768734/in-vitro-efficacy-of-pro-and-anticoagulant-strategies-in-compensated-and-acutely-ill-patients-with-cirrhosis
#2
Ton Lisman, Simone Kleiss, Vishal C Patel, Caleb Fisher, Jelle Adelmeijer, Sarah Bos, Arjuna Singanayagam, Sidsel Hyldgaard Stoy, Debbie L Shawcross, William Bernal
BACKGROUND & AIMS: A simultaneous decline in pro- and anticoagulant drivers in patients with liver diseases results in a 'rebalanced' hemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro- and antihemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound hemostatic changes. METHODS: We tested the effects in vitro of the addition of clinically relevant doses of commonly used pro- and antihemostatic strategies in plasma from healthy individuals (n=30) and patients with compensated (n=18) and acutely decompensated cirrhosis (n=18), and acute-on-chronic liver failure (n=10)...
May 16, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29768547/clinical-outcomes-and-risk-factors-for-death-from-disseminated-histoplasmosis-in-patients-with-aids-who-visited-a-high-complexity-hospital-in-campo-grande-ms-brazil
#3
Barbara Cristina Scarcelli Boigues, Anamaria Mello Miranda Paniago, Gláucia Moreira Espíndola Lima, Maina de Oliveira Nunes, Silvia Naomi de Oliveira Uehara
INTRODUCTION: Disseminated histoplasmosis (DH) is a systemic mycosis caused by Histoplasma capsulatum (H. capsulatum) and is characterized by progressive and fatal evolution in immunocompromised patients. Moreover, it is considered an AIDS-defining disease. METHODS: We performed an observational, analytical, retrospective study to identify the clinical outcomes and risk factors for death from DH in patients with AIDS at an infectious diseases service facility in Brazil between September 2011 and July 2016...
March 2018: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/29764497/activated-prothrombin-complex-concentrate-to-reverse-the-factor-xa-inhibitor-apixaban-effect-before-emergency-surgery-a-case-series
#4
Nina Haagenrud Schultz, Runar Lundblad, Pål Andre Holme
BACKGROUND: The lack of an antidote against factor Xa inhibitors in case of major bleeding or need for urgent surgery is a concern to clinicians. Guidelines on managing major bleeding in patients under anticoagulation with a factor Xa inhibitor suggest several hemostatic agents to reverse the effect, but there is no consensus regarding the choice of drug or appropriate dose. The ability of prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa to reverse the effect of factor Xa inhibitors has been evaluated in animal studies, in vitro studies, and healthy volunteers, but not yet in randomized clinical studies...
May 16, 2018: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29757137/reversal-of-apixaban-induced-alterations-in-haemostasis-by-different-coagulation-factor-concentrates-in-patients-after-hip-or-knee-replacement-surgery
#5
Katrin Schmidt, Kerstin Krüger, Elisabeth Langer, Martin Schmutzler, Elke Johnen, Klaus D Wernecke, Christian Von Heymann, Mareike K Körber
BACKGROUND: Apixaban is a direct oral anticoagulant (DOAC) with a specific inhibition of activated factor X (FXa). In case of bleeding or need of urgent surgery a direct antidote is not yet available. Off-label application of non-specific haemostatic agents, such as prothrombin complex concentrate (PCC) and recombinant FVIIa (rFVIIa), has been reported to reverse the effects of apixaban in in vitro and animal studies. The aim of this study is to measure the reversal potential of PCC and rFVIIa in patients with prophylactic apixaban concentrations...
May 11, 2018: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/29724819/establishing-the-transient-mass-balance-of-thrombosis-from-tissue-factor-to-thrombin-to-fibrin-under-venous-flow
#6
Shu Zhu, Jason Chen, Scott L Diamond
OBJECTIVE: We investigated the coregulation of thrombin and fibrin as blood flows over a procoagulant surface. APPROACH AND RESULTS: Using microfluidic perfusion of factor XIIa-inhibited human whole blood (200 s- 1 wall shear rate) over a 250-μ long patch of collagen/TF (tissue factor; ≈1 molecule per μm2 ) and immunoassays of the effluent for F1.2 (prothrombin fragment 1.2), TAT (thrombin-antithrombin complex), and D-dimer (post-end point plasmin digest), we sought to establish the transient mass balance for clotting under venous flow...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29723892/treatment-regimens-with-bypassing-agents-in-patients-with-hemophilia-a-and-inhibitors-a-survey-from-the-italian-association-of-hemophilia-centers-aice
#7
Antonio Coppola, Massimo Franchini, Giancarlo Castaman, Elena Santagostino, Cristina Santoro, Rita Carlotta Santoro, Massimo Morfini, Giovanni Di Minno, Angiola Rocino
The development of neutralizing antibodies (inhibitors) against infused factor VIII currently represents the main complication of replacement therapy in patients with severe hemophilia A. Inhibitors, indeed, particularly high-titer inhibitors (>5 BU/mL), greatly complicate the management of bleeding, exposing patients to an increased morbidity and mortality risk, thus representing a significant burden for physicians of Hemophilia Treatment Centers (HTCs). Although bypassing agents (i.e., activated prothrombin complex concentrate [APCC] and recombinant activated factor VII [rFVIIa]) are available for the treatment and prevention of bleeding in inhibitor patients, their efficacy, safety, and cost-benefit outcomes are poorly known in the long term and should be further improved...
May 3, 2018: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/29706805/comparison-of-outcomes-in-patients-with-intracranial-hemorrhage-on-factor-xa-inhibitors-versus-vitamin-k-antagonists-treated-with-4-factor-prothrombin-complex-concentrate
#8
Sarah K Harrison, John S Garrett, Kelsey N Kohman, Jeffrey A Kline
The relative clinical efficacy of 4-factor prothrombin complex concentrate (4F-PCC) in oral anticoagulant-associated intracranial hemorrhage is unknown, especially for factor Xa-inhibiting anticoagulants. We report short-term outcomes of patients with oral anticoagulant-associated intracranial hemorrhage on vitamin K antagonists and factor Xa inhibitors who were treated with 4F-PCC. This multicenter, observational study involved patients presenting to the emergency department in nine hospitals in an integrated health care delivery system in Texas between July 2013 and December 2015...
April 2018: Proceedings of the Baylor University Medical Center
https://www.readbyqxmd.com/read/29682191/incidence-and-risk-factors-for-venous-thromboembolism-in-patients-with-pretreated-advanced-pancreatic-carcinoma
#9
Shunsuke Kondo, Mitsuhito Sasaki, Hiroko Hosoi, Yasunari Sakamoto, Chigusa Morizane, Hideki Ueno, Takuji Okusaka
Patients with pancreatic carcinoma are at an increased risk of venous thromboembolism (VTE), which is a major cause of morbidity and mortality in various types of cancer. The aim of this study was to determine the incidence and clinical significance of VTE in patients with pancreatic carcinoma, and to identify biomarkers for the detection of VTE in these patients. The eligibility criteria were chemo-naïve patients with primary pancreatic carcinoma, an Eastern Cooperative Oncology Group performance status of 0-2, and adequate organ function...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29669440/thrombin-generation-assay-detects-moderate-intensity-statin-induced-reduction-of-hypercoagulability-in-diabetes
#10
Hee Sue Park, Ja-Yoon Gu, Hyun Ju Yoo, Se Eun Han, Chan Ho Park, Young Il Kim, Il Sung Nam-Goong, Eun Sook Kim, Hyun Kyung Kim
Statins not only have a lipid-lowering effect but also reduce inflammation and have an antithrombotic effect. Since hypercoagulability assessed by thrombin generation assay (TGA) and increased formation of neutrophil extracellular traps (NET) were demonstrated in diabetes, we investigated whether statin therapy in diabetes modifies coagulation status and NET formation. Twenty-five consecutive patients with diabetes were recruited. Global coagulation assays (prothrombin time [PT], activated partial thromboplastin time [aPTT], and TGA) and NET markers (DNA-histone complex, cell-free DNA, and neutrophil elastase) were measured before and after 3-month moderate-intensity statin therapy...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/29664892/the-role-of-4-factor-prothrombin-complex-concentrate-4-pcc-in-coagulopathy-of-trauma-a-propensity-matched-analysis
#11
Faisal Jehan, Hassan Aziz, Terence O'Keeffe, Muhammad Khan, El Rasheid Zakaria, Mohammad Hamidi, Muhammad Zeeshan, Narong Kulvatunyou, Bellal Joseph
INTRODUCTION: Coagulopathy is a common complication after severe trauma. The efficacy of 4-factor Prothrombin Complex Concentrate (4-PCC) as an adjunct to FFP in reversal of coagulopathy of trauma has not been studied. The aim of our study is to compare 4-PCC+FFP vs. FPP alone for the treatment of COT. METHODS: We reviewed all trauma patients >18y who received PCC+FFP or FFP alone at our Level I trauma center from 2015-16. We excluded patients on preinjury oral anticoagulants...
April 16, 2018: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/29661410/use-of-prothrombin-complex-concentrate-for-management-of-coagulopathy-after-cardiac-surgery-a-propensity-score-matched-comparison-to-plasma
#12
J Fitzgerald, M Lenihan, J Callum, S A McCluskey, C Srinivas, A van Rensburg, K Karkouti
BACKGROUND: An important cause of coagulopathy in cardiac surgery is impaired thrombin generation. While plasma is often used to correct this element of the coagulopathy, studies in vitro suggest that prothrombin complex concentrates (PCCs) might be more effective. Comparative data, however, are scant. METHODS: We compared the outcomes of those who received only plasma with those who received PCCs (with or without plasma) for management of coagulopathy in patients who underwent cardiac surgery with cardiopulmonary bypass at a single institution from 2012 to 2016...
May 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29645406/modified-clot-waveform-analysis-to-measure-plasma-coagulation-potential-in-the-presence-of-the-anti-factor-ixa-factor-x-bispecific-antibody-emicizumab
#13
Keiji Nogami, Tomoko Matsumoto, Yuka Tabuchi, Tetsuhiro Soeda, Nobuo Arai, Takehisa Kitazawa, Midori Shima
BACKGROUND: Emicizumab is an anti-factor (F)IXa/FX bispecific antibody that mimics FVIIIa cofactor function. Emicizumab does not require activation by thrombin and its effect on shortening activated partial prothrombin time (aPTT) is much greater relative to FVIII. The aPTT has limited utility, therefore, in hemophilia A patients (HA-pts) treated with emicizumab. AIM: To evaluate the global coagulation potential of emicizumab. METHODS: Clot waveform analysis (CWA) with prothrombin time (PT)/aPTT-mixed reagents was used to define hemostatic monitoring protocols in HA-pts...
April 12, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29622392/comparison-of-drug-administration-logistics-between-prothrombin-complex-concentrates-and-plasma-in-the-emergency-department
#14
Sumaiah J Alarfaj, Daniel H Jarrell, Asad E Patanwala
BACKGROUND: Prothrombin complex concentrate (PCC) is used as an alternative to fresh frozen plasma (FFP) for emergency bleeding. The primary objective of this study was to compare the time from order to start of administration between 3-factor PCC (PCC3), 4-factor (PCC4), and FFP in the emergency department (ED). The secondary objective was to evaluate the effect of an ED pharmacist on time to administration of PCCs. METHODS: This was a single center three-arm retrospective cohort study...
March 24, 2018: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29619338/three-versus-four-factor-prothrombin-complex-concentrate-for-the-reversal-of-warfarin-induced-bleeding
#15
Tara Holt, Scott Taylor, Prasad Abraham, Wesley Mcmillian, Serena Harris, James Curtis, Tai Elder
Objective: The objective of this study was to evaluate the effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) compared to 4-factor PCC (4F-PCC) in warfarin-associated bleeding. Methods: This multicenter, retrospective, cohort study analyzed data from patients admitted between May 2011 and October 2014 who received PCC for warfarin-associated bleeding. The primary outcome was the rate of international normalized ratio (INR) normalization, defined as an INR ≤1...
January 2018: International Journal of Critical Illness and Injury Science
https://www.readbyqxmd.com/read/29611182/factor-f-viii-viia-enhances-global-haemostatic-function-in-the-co-presence-of-bypassing-agents-and-fviii-among-patients-with-haemophilia-a-with-inhibitor
#16
Keiji Nogami, Tomoko Matsumoto, Koji Yada, Kenichi Ogiwara, Shoko Furukawa, Yasuaki Shida, Masahiro Takeyama, Midori Shima
Bypassing therapy is essential for the haemostatic management of patients with haemophilia A with inhibitor (PWHA-inh), but the therapeutic effects are inconsistent. We previously reported that activated prothrombin complex concentrates (aPCC) activated factor (F)VIIIin vitro, and was mediated mainly by the activated FVII (FVIIa) contained in aPCC. We have extended those studies to assess global coagulation in whole blood from 18 PWHA-inh in the co-presence of aPCC and FVIII using Ca2+ -triggered rotational thromboelastometry...
April 2, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29611104/fixed-dose-4-factor-prothrombin-complex-concentrate-we-don-t-know-where-we-re-going-if-we-don-t-know-how-to-get-there
#17
REVIEW
Scott T Hall, Kyle C Molina
4-Factor Prothrombin Complex Concentrate (4F-PCC) is the standard-of-care intervention in patients with major bleeding taking oral vitamin K antagonists. Despite growing clinical experience with 4-FPCC, the optimal dosing strategy remains unclear. In balancing efficacy, safety, and cost of this treatment, many institutions have adopted a low, fixed-dose regimen, with average doses lower than that in the package insert. The fixed-dose 4F-PCC strategy is supported by the available observational studies and case reports; however, the current body of literature is highly heterogenous...
April 2, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29582334/acquired-hemophilia-a-associated-with-autoimmune-pancreatitis-with-serum-igg4-elevation
#18
Taisuke Narazaki, Shojiro Haji, Yasuhiro Nakashima, Yasuhiro Tsukamoto, Mariko Tsuda, Akiko Takamatsu, Hirofumi Ohno, Takamitsu Matsushima, Tomoko Matsumoto, Keiji Nogami, Midori Shima, Motoaki Shiratsuchi, Yoshihiro Ogawa
A case of acquired hemophilia A (AHA) that developed in a patient with autoimmune pancreatitis (AIP) is presented. A 64-year-old woman was diagnosed with AIP in 2007. The symptoms resolved with prednisolone (PSL). Although the dose of PSL was tapered to 7.5 mg/day for maintenance, serum IgG4 levels remained high. She suddenly presented with subcutaneous bleeding in 2015. Her activated partial thromboplastin time was prolonged (80.0 s). A mixing test showed an inhibitor pattern, factor VIII (FVIII) activity was less than 1%, and FVIII inhibitor was 290 BU/mL...
March 26, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29571739/title-translational-pk-pd-characterization-and-tmdd-modeling-of-an-anti-tfpi-antibody-pf-06741086
#19
Chuenlei Parng, Pratap Singh, Debra D Pittman, Katherine Wright, Beth Leary, Sunita Patel-Hett, Swapnil Rakhe, James Stejskal, Marjorie Peraza, Dawn Dufield, John E Murphy, Robert Webster
Tissue factor pathway inhibitor (TFPI) exhibits multiple isoforms which are known to present in multiple locations such as plasma, endothelium and platelets. TFPI is an endogenous negative modulator of the coagulation pathway, and therefore neutralization of TFPI function can potentially increase coagulation activity. A human monoclonal antibody, PF-06741086, which interacts with all isoforms of TFPI is currently being tested in clinic for treating hemophilia patients with and without inhibitors. To support clinical development of PF-06741086, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06741086 were characterized in monkeys...
March 20, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29569213/prevalence-pathophysiological-mechanisms-and-factors-affecting-urolithiasis
#20
REVIEW
Aslam Khan
The formation of urinary stone, urolithiasis, is one the oldest known disease affecting human throughout different civilizations and times. The exact pathophysiological mechanism of urolithiasis is not yet clear, as these calculi are of various types and too complex for simple understanding. A single theory cannot explain its formation; therefore, different theories are presented in various times for its explanation like free particle, fixed particle, Randall's plaque theory. In addition, various factors and components are identified that play an important role in the formation of these urinary calculi...
March 22, 2018: International Urology and Nephrology
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